Modular microfluidic system

ABSTRACT

A modular microfluidic system is described having at least one base board with a plurality of fluidly linked fluid supply apertures, optional intermediate level boards of equivalent construction, a plurality of microfluidic modules adapted to be detachably attached to the base board/intermediate boards, each having one or more fluid inlets and/or outlets, and a plurality of fluid couplings preferably in the form of projecting ferrules to effect releasable fluid connection between a module and a base board/intermediate level board via a supply aperture on the board and an inlet/outlet on the module. A method of providing a microfluidic system as a modular assembly is also described.

This is a nationalization of PCT/GB03/003853 filed Sep. 5, 2003 andpublished in English.

The invention relates to a microfluidic system having a modularconstruction for rapid assembly and disassembly, and a method ofproviding such a system.

Microfluidic devices and systems have become increasingly important inrecent years for performing large numbers of different chemical and/orbiological operations on a manageable scale, since they allow a largenumber of chemical or biochemical reactions to be carried out as part ofan analytical and/or synthetic process in a relatively small liquidvolume. Such miniaturised analytical or synthetic operations aregenerally more efficient, producing increased response times and reducethe requirement for potentially expensive reagents.

Conventional microfluidic devices and components have been constructedon a chip using technology analogous to that followed in the siliconfabrication industry in general, for example by constructing the devicesin a planar fashion using photolithography and etching techniques.Conventionally, there has been a tendency, in particular by analogy withminiaturisation elsewhere in the silicon industry, to concentratedevelopment efforts on miniaturising onto a single chip of as small asize as possible all chemical, biochemical and biological processingassociated with a particular synthetic and/or analytical process.

Such constructions offer many advantages. However, the resultant chip isrelatively inflexible. It is not always easy to intermix differentmaterials and device technologies within such a single chip. Inspection,maintenance and repair can be complex.

It is an object of the invention to provide a microfluidic system whichoffers enhanced flexibility and which mitigates some or all of thedisadvantages of single chip integral systems.

It is a particular object of the present invention to provide a modularmicrofluidic system in which various different microfluidic componentsare readily assemblable and disassemblable into a complete system tooffer enhanced flexibility and utility.

Thus, according to the present invention in a first aspect there isprovided a modular microfluidic system comprising at least one baseboard having a plurality of fluidly linked fluid supply apertures on oneor both sides thereof, a plurality of microfluidic modules adapted to bedetachably attached to the base board, each having one or more fluidinlets and/or outlets, and a plurality of fluid couplings to effectreleasable substantially fluid-tight fluid connection between a moduleand a base board via a supply aperture on the base board and aninlet/outlet on the module.

Preferably further the system comprises at least one fluid sourceaperture fluidly linked thereto to supply source fluid to the system,and/or at least one fluid output aperture fluidly linked thereto tooutput fluid from the system. Source and/or outlet apertures may beprovided in direct communication to the baseboard or via modules. Aplurality of such fluid source apertures and/or fluid output aperturesmay be provided.

The fluid supply may be gaseous or liquid. More than one fluid may besupplied to any given system.

In accordance with the invention, the microfluidic circuit is built upon the base board, with the system being formed in modular fashion uponthe base board chip, rather than being integrated therewith inconventional manner. Fluid is supplied to the constructed microfluidicsystem via the fluid source aperture in the baseboard or by directintroduction into a module. The base board chip is preferablyconstructed with a pattern of at least partly interconnectingmicrofluidic channels to provide a plurality of fluid channels and/orchambers linking in fluid communication at least some of the supplyapertures to each other and/or to the source aperture. The fluid supplypassages within the modules act in co-operation therewith to complete adesired microfluidic circuit when the modular structure is assembled,the circuit serving to distribute fluid to interconnection points on theboard and hence to the modules. The assembled system may provide aplurality of such circuits functioning in association or independently.

The invention offers significant advantages, particularly in relation toflexibility of construction in use, when compared with prior artsystems. Chip module to base board interconnections may be madeconveniently compact and simple, whilst at the same time connectionsbetween the board and external equipment can utilise well establishedfittings for interfacing to that equipment. Intermixing of differentmaterials and device technology is enabled (for example glass chips on apolymer board). In the same way a choice of external systems such asexternal pumps as well as on-board or module-surface mounted pumps andvalves etc. is offered.

The system of the invention offers flexibility of design choice. Forexample a simple baseboard design may be provided with exchangeablecomplex modules, or complex systems may be included within thebaseboard, with the modules attachable thereto being simple and/ordisposable. Seals and connections between module and board can beselected according to module function.

The overall system provides for simple inspection and maintenance,flexibility of use, and ease of repair to systems, for example byreplacing only a module which is defective rather than an entire system.

A microfluidic module in accordance with the invention comprises one ormore microfluidic devices. As used herein, a microfluidic device maycomprise any known element of a microfluidic system, including withoutlimitation an active device unit, such as a reactor, heater, cooler,analyser, detector, mixer, processor, separator or the like, a fluidfunction unit such as a pump, valve, filter or the like or merely afluid channel, chamber or manifold to complete a particular microfluidiccircuit.

Microfluidic devices in accordance with the invention may be threedimensional or generally planar. In a preferred embodiment, the devicesare generally planar. Each module has a generally planar construction tobe incorporated upon a generally planar baseboard. Inlet/outletapertures are most conveniently provided on one of the planar faces ofsuch a module. Supply apertures are most conveniently provided on aplanar face of the baseboard, and source aperture(s) may be provided atan edge or edge face or the same or opposite planar face thereof.

In particular, each module preferably has a generally planar sandwichconstruction, comprising at least one inner sandwich layer defining afluid channel and/or chamber portion, and at least one cover layercovering and effecting enclosure of the same. In a preferred embodimentthe module comprises at least one sandwich layer defining an enclosedfluid channel and/or chamber portion, for example consisting of pairedsandwich elements into the surface of at least one of which channels arecreated such that the pair assembled together define such an enclosure,with cover layers at either side thereof. Further intermediate layersmay be present.

Active microfluidic elements may be incorporated within the channelsand/or chambers so formed in the sandwich layer or additionally oralternatively may be provided upon the module surface in fluidcommunication with the channel therewithin. One or more inlet and/oroutlet apertures are provided to effect a fluid communication betweenthe channel and an external surface of the module, for fluid connectionto the baseboard. A baseboard may be similarly constructed.

The base board and of the modules may be fabricated conveniently insuitable plastics material. They may be constructed from monolithicblocks of material, from sandwich layers as above described, or fromthin layer laminates or combinations thereof. Layers or materials whichcontact fluid in use are preferably fabricated when necessary fromchemically resistant plastics material, such as epoxy, a photoimagableepoxy being most preferred. Suitable resistant thin film laminatematerials might include epoxy glued PEN laminates. This gives goodresistance with good fabricability of fluid channels and chambers. Insandwich structures, cover layers including fluid inlet/outlet portswhich might also contact fluid in use are also preferably fabricatedfrom materials exhibiting good chemical resistance, for example epoxy orother plastics such as polyetheretherketone (PEEK). Alternatively,materials may be given a suitably resistant coating in such areas.

Chemical properties of merely structural cover or intermediate layersmight be less critical. Likewise material selection might be lesscritical for components intended for use with fluids presenting a lessharsh environment. In these cases less resistant materials such as PMMA,PET, acrylic polymers and the like might be suitable.

Additionally, any materials or layers and in particular cover layersmight also be modified for specific properties, for example fortransparency, for electrical, magnetic or dielectric properties, toprovide mountings for externally mounted microfluidic device componentsetc. Metallic layers may be provided or incorporated, for example toserve as a conductor, resistive heater or otherwise.

In practice, different parts of individual components might havedifferent functional requirements, for example regarding transparency,structural strength, chemical resistance etc. Combinations of materialsmay be used, for example using a combination of materials and componentsand by using composite substrates for the baseboard and modules toachieve the best combination of properties.

For example, in the case of a microchemical reactor it is beneficial touse a substrate polymer that is optically transparent to enable easyinspection of the fluid path and/or to allow measurements and/or isthermally transparent or transparent at other wavelengths for anypurpose. It will be understood however that a readily available polymerwith good transparency that is also resistant to a wide range ofsolvents used in synthetic chemistry is not generally available. Byadopting a composite approach a substrate can be readily formedcomprising a composite structure having areas of a transparent material(not necessarily exhibiting high chemical resistance) where required,and areas of a chemically resistant material (not necessarily exhibitinghigh transparency) at least in regions where solvent contact ispossible, preventing contact with the less resistant transparentsubstrate material. For example a basic structure comprises transparentmaterial but in which inserts of chemically resistant material areincluded in the substrate in regions where solvent contact is possible.Alternatively a basic structure of chemically resistant material with“window” inserts of transparent material will serve the same purpose.Specific areas with other functionality will similarly readily suggestthemselves.

As used herein, microfluidic will be understood to refer tomicrostructures having at least some sub-millimeter dimensions,microstructure in this case being used to refer to any of a variety ofwell known structures in such systems, including, but not limited to,the channels and chambers hereinabove described, that are capable ofproviding passage or storage for a fluid.

In accordance with the invention, a plurality of fluid couplings areprovided to effect a fluid-tight connection between at least one fluidsupply aperture on a base board and at least one inlet/outlet on amicrofluidic device module. Fluid tight connection is preferablyeffected by interference fit between a coupling and a supply aperture,and couplings and apertures are sized and materials for theirfabrication selected accordingly, for example being flexibly resilientat least in the region of connection.

This interference fit alone may be sufficient to maintain a fluid-tightconnection, at least in use under action of supplied fluid pressure.Alternatively connecting means may be provided to hold the assemblytogether in use and assist in maintenance of a fluid-tight connectionbetween modules and board by urging coupling and aperture into closerassociation and retaining thereat with a suitable urging force. Suchconnecting means may for example comprise spring clips, screws, bolts,clamps or like mechanical fixings. The connecting means connect modulesand board together. There is no need for specific connecting meansseparately associated with each coupling/aperture connection. One or afew mechanical fasteners can be used to hold together a system makingmultiple fluid connections.

These connecting means will typically be releasable as it is a featureof the invention that modules are readily assembled into multipleconfigurations and are able to be dissasembled by a user for example forreassembly into other configurations. However it will be appreciatedthat in certain circumstances the user may wish to use more permanentfixings to retain coupling and aperture in fluid-tight association on asemi-permanent or permanent basis, for example by permanent mechanicalfixing or gluing, and a system in accordance with the invention allows auser to choose to do this.

Conveniently, the connection comprises a releasable coupling, forexample in the form of a channel means removably insertable into asuitable recess in such a inlet/outlet/aperture to effect a fluid tightcommunicating connection therebetween. Such channel means convenientlycomprises a tubular element, in particular a rigid tubular element, forexample being parallel sided, for example being square or rectangular,polygonal, or alternatively having a circular or elliptical crosssection, with any recess into which such a tubular element is to bereceived preferably being shaped accordingly.

Such a tubular element can be a separable and distinct unit. However,for convenience, particularly in relation to the preferred embodimentwhere base board and module comprise generally planar components, thetubular element preferably comprises a projecting ferrule integral withand projecting from a first aperture comprising either a fluid supplyaperture in the base board or an inlet/outlet in the module, and adaptedto be received in a recess comprised as a second aperture,correspondingly either an inlet/outlet in the module or a supplyaperture in the base board. In particular the ferrule projects generallyperpendicularly from a generally planar surface, to effect a fluidconnection between a base board and module adapted to lie generallyparallel when connected.

In a most preferred form, ferrules are provided which project above thesurface of the base board to be received within recesses comprising theinlet/outlet apertures of modules to be attached thereto.

Ferrules as above described can offer particular advantages. The ferrulesystem enables dead volume in fluid path between “chips” to beminimised. Use of ferrules allows higher density of interconnectionsthan other fittings such as high-pressure liquid chromatography (HPLC)fittings and the like. Ferrules can withstand high pressures. Ferrulesgenerally require a reduced thickness of material in which to be heldcompared to the thickness needed to hold a screw thread or like fitting,allowing much thinner layers, down to layers essentially comprisingfilms, to be interconnected. One or a few mechanical fasteners can beused to hold together a system making multiple fluid connections throughthe ferrules.

The ferrules ensure accurate mechanical alignment of fluid elementsmaking accurate module placement easy.

It is generally easy to machine suitable ferrule recesses within thematerials typically envisaged for use for baseboard and modules, givingscope for a range of ferrule and recess shapes. The internal bore andexternal diameter can be varied within limits, making it possible forthe ferrule to incorporate microfluidic functionality. For example theinternal bore could incorporate a filtration function, optionallycomprising multiple holes (in manner analogous to a photonic crystal).For example the ferrule can be modified to a larger shape to include areservoir function.

Optionally the fluid coupling can incorporate additional functionalityin that it includes within a fluid channel therewithin a fluidly activecomponent, rather than serving merely as a channel. The fluid couplingcould contain a non-return valve, for example a ball valve. The ballvalve could conveniently be magnetically switchable valve. The fluidcoupling could contain a catalyst frit or could incorporate a filter.Various switches could be conceived.

It is possible to use a conducting for example metallic fluid couplingsuch as a metallic ferrule to effect an electrical as well as a fluidinterconnection between modules and/or boards. Such a metallic couplingmay optionally be provided with an insulating layer on a fluid and/ormodule contacting surface, effecting an electrical contact betweenmodules and/or electrical contact with fluid therein. A ferrule baseddesign offers particular flexibility in that the system may readily beprovided with further functional interconnections (eg magnetic, optical)either integral with or separately from the ferrule.

Optionally the ferrule can incorporate or be provided with a closure forclosing a pathway not being used in a particular device combinationallowing redundancy in pathway choice in base board for example duringplug and play use. The closure may comprise a bung to be applied by auser, or an integral closure valve adapted to be operated manually, orto operate automatically on insertion of ferrule into recess.

The invention hereinabove has been described in terms of a singlebaseboard with a plurality of modules disposed in a single layerthereupon. It will be readily appreciated that the invention is not solimited. A particular flexibility of the invention is that it allows formulti-level stacking of modules and/or primary base boards and/orintermediate level boards. Such intermediate level boards may servemerely to provide fluid connections in the form of channels, chambers orthe like, or may also include active microfluidic components. Similarly,it will be understood that the invention encompasses modular structurescomprising a plurality of modules as hereinbefore described and at leastone primary base board, in which the base board is also optionallyprovided with active microfluidic components.

References hereinabove to features of the primary baseboard will beunderstood to be equally applicable to such intermediate level boards.Intermediate level boards may be constructed as above described andpreferred features thereof will be construed by analogy. In particular,boards are preferably planar, and preferably of a sandwich constructionas above.

In embodiments comprising such a multi-level stacking system, anycomponent adapted for use at an intermediate level will comprise atleast one inlet aperture on a first “lower” surface and at least oneoutlet aperture on a second “upper” surface (it being understood thatlower and upper are being used herein as a convenience to refer tosurfaces proximal and distal to the base board, and not to imply anyrestrictive orientation). References herein to inlets/outlets in amodule will be understood to apply equally where appropriate to such alower aperture, and references herein to a base board fluid supplyaperture will be understood to apply equally where appropriate to suchan upper aperture in an intermediate level component. It is particularlyeasy to stack multiple layers using the preferred ferrule embodiment.

In a preferred embodiment, fluid connections are effected by projectingferrules between components adapted to lie generally parallel. Inmulti-level systems, it will be convenient that these ferrules allproject in the same direction. In particular, ferrules are preferablyprovided at apertures in the upper surface of the base board and atapertures in the upper surface of all intermediate level modules, to bereceivingly engaged in fluid tight connection within recessed portionsat apertures on the lower surface of all intermediate level componentsand all top level components.

Attachment of a module to the board, or of an upper layer module, to alower layer module in multi-layer systems, may be achieved by anysuitable releasable attachment means, including without limitationscrews or screw fixings, bayonet fittings whether quick release or not,push and snap fit connectors, vacuum or mechanical clamping connections,releasable mutually engageable resilient hook and felt pads, hooks,clips etc. The fluid couplings themselves, especially in the preferredform as channel means in interference fit between pairs of linkedapertures, for example ferrules engaged in interference fit in recesses,may assist in or even suffice to constitute such mechanical connection.However, additional mechanical connectors will usually be preferred.

The system in accordance with the invention provides a plurality ofinterchangeable elements enabling a plurality of different microfluidicfunctions to be performed, on one or more levels.

In accordance with the invention in a further aspect a method ofproviding a microfluidic system as a modular assembly comprisesassembling the system above described. In particular the methodcomprises the steps of:

providing at least one base board having a plurality of fluidly linkedfluid supply apertures on one or both sides thereof and a plurality offluid channels and/or chambers lining in fluid communication at leastsome of the supply apertures;

providing a plurality of microfluidic modules, each having one or morefluid inlets and/or outlets and at least one fluid channel or chamber influid communication therebetween;

connecting the modules to the base board via fluid couplings adapted toeffect releasable fluid-tight connection therebetween via a supplyaperture on the base board and an inlet/outlet on the module;

such that the fluid channels or chambers within the modules act inco-operation with fluid channels or chambers in the baseboard tocomplete a desired microfluidic circuit.

Other features of the method will be understood by analogy.

The invention will now be described by way of example only withreference to FIGS. 1 to 8 of the accompanying drawings wherein:

FIG. 1 illustrates in cross section how fluid connection is effectedbetween components in accordance with the invention;

FIG. 2 is a schematic illustration of a simple basic construction of amicrofluidic device for use with the invention;

FIG. 3 is an example microreactor system employing the principles of theinvention;

FIG. 4 is a plan view of the baseboard of the reactor of FIG. 3;

FIG. 5 is an on chip manifold from the reactor of FIG. 3;

FIG. 6 is a plan view of a first active microfluidic device from thereactor of FIG. 3;

FIG. 7 is a plan view of a second active microfluidic device from thereactor of FIG. 3;

FIG. 8 is plan view of a third active microfluidic device from thereactor of FIG. 3;

FIGS. 9 and 10 are examples of composite microfluidic device/substratearrangements using a combination of materials to achieve the bestcombination of properties;

FIGS. 11 and 12 are examples of reactor chip arrangements employing thecomposites of FIGS. 9 and 10.

FIG. 1 illustrates in cross section the basic design of fluid connectionin accordance with the preferred embodiment of the invention employingprojecting ferrules.

Illustrated schematically in FIG. 1 are a baseboard (1), a first levelcomponent layer (2) and a second level component layer (3). The threelayers are shown in exploded view disassembled but aligned for assembly.

Fluid connection within the system is effected by insertion of ferrules(7, 9) respectively provided at an upper supply aperture in the baseboard (1) and at an upper outlet aperture in the first level board (2)which are received in the recesses (6, 8) respectively provided in alower surface of the first level board (2) and in a lower surface of thesecond level board (3). In the embodiment, the connection employs simpleparallel-sided holes to take PTFE tubes forming the ferrules (7, 9)although it will be understood that more complex holes and ferrules arepossible. The ferrules are retained within the holes in interference fitto provide a fluid tight leak proof connection.

In the example shown fluid supply is effected via an inlet fluid sourceaperture (10) comprising flexible tubing (11) of 1/16 inch (1.5 mm)diameter retained within HPLC fittings (12). The fluid path is shown bythe dark line (14).

To assemble the modular structure into a laboratory system, a mechanicalload is applied in the direction of the arrows (L) to effect engagementbetween the ferrules (7, 9) and the recesses (6, 8). Additionalmechanical fixings (not shown) might be provided to ensure a more securemechanical connection between the components (1, 2, 3).

A simple schematic device construction is illustrated in the explodedview in FIG. 2. The example device has a sandwich layer structurecomprising an external base layer (21) of polyetheretherketone (PEEK), apair of inner layers (22) of photoimagable epoxy and an upper layer (24)of polymethylmethacrylate (PMMA) and internal layers (22). Channel means(23) are provided in the inner epoxy sandwich layer (22) to provide thenecessary microfluidic microstructure. Fluid ports (24) through theupper layer (24) give a fluid communication from a surface of thecompleted device to the channel means (23) which form enclosed internalchannels once the two parts illustrated in the exploded view of FIG. 2are assembled.

The sandwich layer elements (22) and upper layer (24) contact fluid inuse, respectively in the channels (23) and ports (25). Accordingly theseare fabricated from materials exhibiting good chemical resistance, inthe example respectively photimagable epoxy and PEEK. Properties of themerely structural lower layer (21) are less critical.

The simple schematic in FIG. 2 does not illustrate any activemicrofluidic devices. It will be understood that these could beincorporated suitably within the channels themselves (for example inparticular if these take the form of pumps, valves, filters or the like)or could be incorporated on a module surface in fluid communication withthe channels (23).

A microfluidic reaction system in accordance with the invention isillustrated in plan view in FIG. 3. The reactor comprises inlets for twosupply fluids (“fluid A” and “fluid B”), and provides for threeprocessing streams (“stream 1”, “stream 2”, “stream 3”).

The reactor comprises a baseboard (31) incorporating a plurality offluid supply channels (32) therewithin. The base board has a number ofmicrofluidic components mounted thereupon, being a manifold (34) tosplit the supply fluid (A, B) into the three streams (streams 1, 2, 3),and then within each stream a series of modules comprising a mixer chip(35), a detector chip (36), a reactor chip (37) and a further detectorchip (36). These components are shown separately in FIGS. 4 to 8.

A system constructed in accordance with the principles of the inventionas illustrated by FIG. 3 offers admirable simplicity and flexibility,providing a number of advantages over conventional designs. Inparticular it enables use of larger interconnect components and scalingfrom the macro to the micro world by microfluidic “fanning” (transitionfrom large pitch to small pitch spacing between fluidic channels).Fittings from chip to board enable close packing of interconnections on<2 mm square packed spacing or <1 mm staggered spacing.

FIG. 4 illustrates in plan view the baseboard (31) of FIG. 3 without thecomponents attached. The fluid channel means provided within thebaseboard (32) are illustrated more clearly.

The manifold (34) of FIG. 3 is illustrated in greater detail in planview in FIG. 5. It can be seen from FIG. 5 how the manifold receivesfrom a single inlet the two fluids (fluid A, fluid B) and produces 6outlets, 1 to 6, effecting a paired supply of fluid A and fluid B to thethree streams illustrated in FIG. 3.

The device is constructed in accordance with the principles of FIG. 2.Channel size in the example is 150 μm by 50 μm. Routing is effectedthrough 300 μm channels. The overall size of the device is 62 by 72 by 4mm.

FIG. 6 illustrates in side view (above) and plan view (below) the micromixer chip of FIG. 3. The micromixer chip receives two fluid streamscomprising fluid A and fluid B respectively in inlet A and inlet B.These are mixed together as they follow the flow channel (41) to theoutlet. The chip is of a basic design as illustrated in FIG. 2, with achannel size of 100 μm by 50 μm and an overall size of 45 by 25 by 4 mm.It is retained in position on the baseboard by means of the clamp (42).

FIG. 7 is a representation of a reactor chip (37) from FIG. 3 shown inside view (above) and plan view (below). Fluid flows from inlet tooutlet via the flow channel (51) thereby passing through the reactorportion (53). The reactor portion comprises a catalyst bed (54) 3 mm indiameter and 2 mm deep retained by the screw in plug (55). The overallassembly has a channel size of 100 μm by 50 μm, an overall size of 36 by25 by 6 mm, and is retained in position by the clamp (52).

FIG. 8 illustrates the detector chip (36) of FIG. 3 in side view (above)and plan view (below). Fluid flows from inlet to outlet via the flowchannel (61).

The detector's active area (68) includes a light source in the form ofan LED (63) or an optical fibre (not shown) to an external source, adiffraction grating (64) and a light collector in the form of theoptical fibre (65). A lens (66) in front of the light source collimatesthe light and a lens (67) in front of the light collecting fibreimproves the light collection efficiency. Collected light is sent forspectral analysis.

Additional electrical detection function is provided via groups of 3gold microelectrodes (69), 110 μm wide on 200 μm pitch. Channel size is400 μm by 400 μm, giving an overall device dimension of 50×30×5 mm.

It has been noted that systems in accordance with the invention can begiven enhanced functionality by using a combination of materials andcomponents and by using composite substrates for the baseboard and chipsto achieve the best combination of properties.

For example, in the case of a microchemical reactor it is beneficial touse a “window” substrate polymer that is transparent to enable easyinspection of the fluid path, but in which inserts are included in thesubstrate in the regions where solvent contact is possible; preventingcontact with the “window” substrate.

An example of such a composite structure is given in FIG. 9. In thefigure different materials are represented by different shading,comprising, in accordance with the illustrated key:

71—Baseboard substrate material (e.g. PMMA);

72—Chip substrate material (e.g. PMMA)

73—photoimagable epoxy

74—Chemically resistant inserts (e.g. PEEK)

75—Ferrules (e.g. PTFE)

76—Fluid connector (e.g. PEEK)

The insert is simply a cylinder traversing the substrate through whichis drilled a fluid path way and recess to support a ferrule. Thematerial of the insert can be chosen from high chemical resistancepolymers such as PEEK or PTFE or in a curable resin formed bymicromoulding or lithographically using a photoformable resin. Theinserts can be produced by any method including machining or injectionmoulding.

More complex inserts might have the ferrule integral with the insert.Although this would inhibit ferrule replacement it may be a good optionfor large arrays of chips where multiple ferrule insertion would be timeconsuming. This is illustrated by the elements 77 in FIG. 10, whereotherwise like numerals are used for like materials.

The concept of using a composite approach to achieve the requiredproperties at the optimum location can also be extended to themicrofluidic channel walls. The surface properties of the walls shouldideally be matched to the desired flow characteristics of the materialbeing transported by the channel. For example, if low wall contactresistance is required a low surface energy coating is a more convenientmethod of achieving the desired effect compared to producing the wholesystem in a low surface energy polymer. For example, a photoimagableepoxy treated with Fluorolink S10 (Ausimont)—a di-triethoxysilane basedon a linear perfluoropolyether backbone reduces the surface energy to 13dynes/cm. Conveniently the walls of the channels can alternatively betreated to make them hydrophilic or hydrophobic or to providebiocompatibility etc.

A further benefit of the interconnected baseboard and processor chipconcept underlying the present invention is the possibility ofapplication to scale up by scale out. Scale out is the term oftenapplied to increasing output from a processor chip performing, forexample, a synthetic procedure by multiplying the number of processorchips. This preserves the reaction conditions for the channel dimensionsoptimised for a single process or series of processes which wouldotherwise change if the channel dimensions were increased to achievehigher throughput. This can be achieved by the baseboard functioning asa manifold, supplying reagents to an array of processor chips. Themanifold can provide a single sided input to multiple outputs from eachprocessor chip). A manifold on one side can provide an interdigitatedinput and output array of channels or one side can provide an inputmanifold and a higher level board can provide an output manifold

Examples of such arrangements exploiting the composite concept are shownin FIGS. 11 and 12, respectively illustrating the use of a baseboard asa manifold for supplying fluid in parallel to an array of processorswith multiple outputs from each processor chip and the use of baseboardsas input and output manifolds for feeding processor chips in parallelfor scale up by scale out or by processor replication. The shading keyof FIGS. 9 and 10 is applied to the systems illustrated in FIGS. 11 and12.

The interconnection system provides a ready means of developingprocesses by series interconnection of each operation with optimisationof each operation readily achieved by exchange of chips. Once a seriesof operations are optimised they can be conveniently integrated into asingle chip and then if required converted into arrays with thebaseboard providing multiple feeds for use in high throughput screeningor the baseboard serving as input and output manifolds for processreplication to scale up or achieve increased throughput by scale out. Inthis way very large numbers of chips can be arrayed to achieve aproduction capability.

The complete system can be a complete hybrid of materials with forexample the baseboard manifold being in polymer, the ferrule seals inpolymer, the processor chips in glass, the pumping and valving system inmetal possibly with internal polymer seals etc.

1. A modular microfluidic system comprising at least one base boardhaving a plurality of fluidly linked fluid supply apertures on one orboth sides thereof, a plurality of microfluidic modules adapted to bedetachably attached to the base board, each having one or more fluidinlets and/or outlets, and a plurality of fluid couplings to effectreleasable fluid-tight connection between a microfluidic module and theat least one base board via a supply aperture on the at least one baseboard and an inlet/outlet on the microfluidic module, said fluidcoupling comprising a ferrule insertable into a suitably shaped recessin such an inlet/outlet/aperture to effect a fluid tight communicationtherebetween, said ferrule projecting from a surface of one of said baseboard and microfluidic module in a direction toward a surface of theother of said base board and microfluidic module and being resilient atleast in the region of fluid-tight connection between said ferrule andrecess.
 2. A modular microfluidic system in accordance with claim 1wherein any recess into which said ferrule is to be received is shapedaccordingly.
 3. A modular microfluidic system in accordance with claim 2wherein the ferrule is integral with, and projects from, a firstaperture comprising either a fluid supply aperture in the base board oran inlet/outlet in a microfluidic module, and said ferrule is adapted tobe received in a recess comprised as a second aperture, correspondinglyeither an inlet/outlet in a microfluidic module or a supply aperture inthe base board.
 4. A modular microfluidic system in accordance withclaim 1 wherein the ferrule projects generally perpendicularly from agenerally planar surface of the base board, to effect a fluid connectionbetween a base board and module adapted to lie generally parallel whenconnected.
 5. A modular microfluidic system in accordance with claim 1further comprising at least one fluid source aperture fluidly linkedthereto to supply source fluid to the system, and/or at least one fluidoutput aperture fluidly linked thereto to output fluid from the system.6. A modular microfluidic system in accordance with claim 1 wherein thebase board is constructed with a pattern of interconnecting microfluidicchannels to provide a plurality of fluid channels and/or chambers in uselinking in fluid communication at least some of the supply apertures toeach other and/or to the source aperture.
 7. A modular microfluidicsystem in accordance with claim 1 wherein each microfluidic module has agenerally planar construction to be incorporated upon a generally planarbase board.
 8. A modular microfluidic system in accordance with claim 1wherein different parts the at least one base board and/or microfluidicmodules are fabricated from different materials.
 9. A modularmicrofluidic system in accordance with claim 1 wherein a connectingmeans is provided to hold the assembly together in use and assist inmaintenance of a fluid-tight connection by urging ferrules andcorresponding recesses into closer association and retaining thereatwith a suitable urging force.
 10. A modular microfluidic system inaccordance with claim 1 wherein the ferrule is a metallic ferrule toaffect an electrical as well as a fluid interconnection.
 11. A method ofproviding a microfluidic system as a modular assembly comprising thesteps of: providing at least one base board having a plurality offluidly linked fluid supply apertures on one or both sides thereof and aplurality of fluid channels and/or chambers linking in fluidcommunication at least some of the supply apertures; providing aplurality of microfluidic modules, each having one or more fluid inletsand/or outlets and at least one fluid channel or chamber in fluidcommunication therebetween; providing a fluid coupling comprising aferrule insertable into a suitably shaped recess in such aninlet/outlet/aperture to effect a fluid tight communicationtherebetween, said ferrule projecting from a surface of one of said baseboard and microfluidic module in a direction toward a surface of theother of said base board and microfluidic module and being resilient atleast in the region of fluid-tight connection between said ferrule andsaid recess; connecting the microfluidic modules to the at least onebase board via the flexibly resilient ferrule to effect releasablefluid-tight connection therebetween via a supply aperture on the atleast one base board and an inlet/outlet on the microfluidic module suchthat the fluid channels or chambers within the microfluidic modules actin co-operation with fluid channels or chambers in the at least one baseboard to complete a desired microfluidic circuit.
 12. A modularmicrofluidic system in accordance with claim 1, wherein the ferrule is aPTFE tube.